Validation of the cell cycle G2 delay assay in assessing ionizing radiation sensitivity and breast cancer risk

Genetic variations in cell cycle checkpoints and DNA repair genes are associated with prolonged cell cycle G2 delay following ionizing radiation (IR) treatment and breast cancer risk. However, different studies reported conflicting results examining the association between post-IR cell cycle delay and breast cancer risk utilizing four different parameters: cell cycle G2 delay index, %G2–M, G2/G0–G1, and (G2/G0–G1)/S. Therefore, we evaluated whether different parameters may influence study results using a data set from 118 breast cancer cases and 225 controls as well as lymphoblastoid and breast cancer cell lines with different genetic defects. Our results suggest that cell cycle G2 delay index may serve as the best parameter in assessing breast cancer risk, genetic regulation of IR-sensitivity, and mutations of ataxia telangiectasia mutated (ATM) and TP53. Cell cycle delay in 21 lymphoblastoid cell lines derived from BRCA1 mutation carriers was not different from that in controls. We also showed that IR-induced DNA-damage signaling, as measured by phosphorylation of H2AX on serine 139 (γ-H2AX) was inversely associated with cell cycle G2 delay index. In summary, the cellular responses to IR are extremely complex; mutations or genetic variations in DNA damage signaling, cell cycle checkpoints, and DNA repair contribute to cell cycle G2 delay and breast cancer risk. The cell cycle G2 delay assay characterized in this study may help identify subpopulations with elevated risk of breast cancer or susceptibility to adverse effects in normal tissue following radiotherapy

Improving the Clinical Treatment of Vulnerable Populations in Radiation Oncology

The increasing role of radiation oncology in optimal cancer care treatment brings to mind the adage that power is never a gift, but a responsibility. A significant part of the responsibility we in radiation oncology bear is how to ensure optimal access to our services. This article summarizes the discussion initiated at the 2019 American Society for Radiation Oncology Annual Meeting educational panel entitled "Improving the Clinical Treatment of Vulnerable Populations in Radiation Oncology: Latin, African American, Native American, and Gender/Sexual Minority Communities." By bringing the discussion to the printed page, we hope to continue the conversation with a broader audience to better define the level of responsibility our field bears in optimizing cancer care to the most vulnerable patient populations within the United States

CNS Tumors in Children

Pediatric CNS malignancies represent 20% of all pediatric malignancies, and approximately 3,000 cases occur in the United States annually. CNS malignancies are the most frequent tumors in childhood after hematological malignancies and require a multidisciplinary management. Surgery, chemotherapy, and radiation therapy play a prominent role in the management of nearly all pediatric CNS malignancies; however, the selection of treatment is based on the pathology as well as the extent of the disease

Postmastectomy radiation for stage ll breast cancer patients with T1/T2 lesions

175 Background: Post mastectomy radiation (PMR) is usually recommended for T3 or N2 breast cancer (BC). The role of PMR for stage ll BC with T1/T2 lesions remains controversial. The aim of this study was to assess the role of PMR in this subgroup of patients. Methods: A retrospective analysis of a prospectively collected database of all stage ll BC patients treated with mastectomy at our institution between 2005-2008 was performed. Demographics, tumor stage, histology, receptor status, adjuvant therapy, nodal status, failure patterns and disease free survival rates (DFS) were compared between the patients who received PMR vs.those who were not radiated. Results: Eighty-two patients underwent mastectomies for stage II disease with a T1/T2 lesion. Twenty two of those (27%) received PMR. The average follow up time was 47 months. The patients in the PMR group had significantly larger tumors (90% vs. 64%), more advanced stages (55% vs. 17%) and higher grade histology (59% vs. 32%). Menopausal status, nodal disease, histology, multifocality and receptors status did not differ significantly between the groups. Three patients in the non radiated (NR) group had a distant recurrence compared to 2 patients in the PMR group. There was one contra-lateral cancer in the NR group. The overall DFS was 86.6% in the NR group vs.91% in the PMR group, (p=0.72). Four patients had a chest wall recurrence (CWR) in the non-radiated (NR) group compared to none in the PMR group; however this was not statistically significant. In a sub-groups analysis comparing only T2, Stage IIB and high grade tumors respectively between the PMR and NR groups there was also no statistical difference in local or distant recurrence and in DFS. In the NR group, high grade tumors (p=0.0024) and estrogen receptors (ER) negativity (p=0.0168) were prognosticators of CWR. Conclusions: In our series PMR did not result in a statistically improved outcome for stage ll BC with T1/T2 lesions. A prospective trial randomizing patients with high grade or ER negative tumors only between PMR vs. NR could further clarify the role of PMR for stage II (T1/T2) lesions